With the increase in the smoking population and the aggravation of air pollution, lung cancer cases have rapidly increased in South Korea. A Korean statistical report has it that lung cancer cases rank first after stomach cancer in men and come next after breast cancer, uterine cancer, stomach cancer and colorectal cancer in women, and is associated with the highest rate of mortality in both men and women.
The frequency of incidence of lung cancer and the mortality rate from lung cancer in Korea are expected to increase for a significant period of time in the future in light of the current trend of an increasing smoking rate. As cancerous cells grow, the lung cancer causes various symptoms including vascular invasion into adjacent tissues, airway blockage, metastasis to lymph nodes, etc. Approximately 10-15% of lung cancer cases absent of any symptoms are diagnosed during a regular checkup. In most cases, lung cancer, when diagnosed, has already progressed to stage III or beyond, so that they are, for the most part, difficult to cure. Therefore, the early diagnosis of lung cancer is presenting itself as an urgent problem to be solved so that the mortality from lung cancer can be reduced.
Various methods are used in combination to diagnose lung cancer. So far, a number of lung cancer screening tests have been employed, including examination of tumor size, metastasis to lymph nodes, immunohistochemistry of biopsy samples of tumerified lung tissue or lymph nodes, chest X-ray screening, chest computerized tomography, and bronchoscopy. Lung cancer shows up in chest computerized tomography only if the size of the tumor is 0.1 cm or larger. However, lung cancer by this time has probably already metastasized to other tissues. In bronchoscopy, the inside of the lung can be directly observed with an endoscope, but there is the problem of spatial limitation that makes it difficult to observe tumors in deep places.
To supplement such lung cancer screening methods, attempts have been made to use the levels of CBC (complete blood count), serum electrolytes (including calcium), alkaline phosphatase, albumin, AST (aspartate aminotransferase), ALT (alanine transaminase), total bilirubin or creatinine, to diagnose lung cancer. Although studied for their values as diagnosis or prognosis factors, the application of conventional tumor markers is accompanied by limitations, and there are no officially recommended lung cancer markers.
Haptoglobin (Hp) is a protein that is redundantly found in the blood, like albumin. The serum protein is synthesized mainly in hepatocytes, dermal cells, pulmonary cells and renal cells and released into the blood. It exists as a tetrameric protein consisting of two α- and two β-chains, connected by disulfide bridges. In blood plasma, haptoglobin binds free hemoglobin released from erythrocytes and thereby inhibits its oxidative activity (Wassell J.(2002) Haptoglobin: function and polymorphism. Clin Lab. 46, 547-552/Langlois M. R. & Delanghe J. R. (1996) Biological and clinical significance of haptoglobin polymorphism in humans. Clinical Chemistry 42, 1589-1600). A recent research report on proteomic research showed that haptoglobin, although in a very small amount, is released from subcutaneous and abdominal adipocytes. The protein is synthesized in the adult liver, but not in the fetal liver. Haptoglobin is an acute phase protein (APP), whose plasma level rapidly increases in response to any infection or inflammatory process.
Haptoglobin exists in two allelic forms in the human population, so-called Hp1 and Hp2, the latter having arisen due to the partial duplication of Hp1 gene. Three genotypes of Hp, therefore, are found in humans: Hp1-1, Hp2-1, and Hp2-2 (Maeda N, McEvoy S M, Harris H F, Huisman T H, Smithies O. (1986) Polymorphisms in the human haptoglobin gene cluster: chromosomes with multiple haptoglobin-related (Hpr) genes. Proc Natl Acad Sci USA. 83, 73957399/Patzelt D, Geserick G, Schroder H. (1988) The genetic haptoglobin polymorphism: relevance of paternity assessment. Electrophoresis 9, 393397). There are two Hp alpha chain (Hpα) isoforms: alpha 1 and alpha 2. These alpha proteins exist as position variants in various species (Sadrzadeh S M, Bozorgmehr J. (2004) Haptoglobin phenotypes in health and disorders. Am J Clin Pathol. 121 Suppl: S97-104).
Among the diseases associated with the gene for the protein are diabetic nephropathy and Crohn's disease. As haptoglobin is indeed an acute-phase protein, any inflammatory process such as infection, extreme stress, burns, major crush injury, allergy, etc. may increase the levels of haptoglobin in the plasma. A recent report demonstrates that patients with cancer including ovarian cancer have elevated levels of plasma haptoglobin.
However, much study must be done to examine whether heptoglobin can act as a diagnostic marker for lung cancer. Accordingly, there is a need for a marker by which lung cancer can be specifically diagnosed and prognosticated.